The overuse of antibiotics fuels the antimicrobial resistance (AMR) dilemma, which has complicated clinical treatment of bacterial illnesses and jeopardized worldwide public health. Action must be taken immediately to address the AMR issue.
As novel antimicrobial agents, bacteriophages (phages) and their lytic enzymes have been extensively explored. Phages are the most prevalent biological entities, which are found in every part of the biosphere, including soil, the atmosphere, marine ecosystems, and the human body.
The ability of phages to specifically infect and rapidly destroy their hosts during their lytic life cycles is a notable advantage over antibiotics. Endolysins are lytic enzymes produced by phages to degrade the bacterial cell wall, thereby releasing replicated progeny virions. For billions of years, phages have utilized endolysins for this specific function. This makes endolysins strong candidates for use as alternatives to antibiotics.
Synthetic biology has been employed to improve the specificity and catalytic activity of endolysins by fusing them with various antimicrobial peptides and by swapping or shuffling between different endolysins. Engineered endolysins have significant potential for in vitro applications. In vivo uses, however, demonstrate varying levels of therapeutic effectiveness.
While several endolysins have been successful in topical treatments, such as for skin bacterial infections, the systemic use of endolysins remains challenging. Endolysins are easily degraded by stomach acids and proteases when taken orally. Another issue with systemic and mucosal administration is the adverse immunological response triggered by the production of neutralizing antibodies, which could reduce endolysin activity in vivo.
Further exploration of endolysins is required to overcome these obstacles and to support their clinical applications in vivo. Endolysins encapsulated in liposomes or alginate hydrogels using nanoparticles may be a feasible solution to overcome the delivery challenges.
This research topic explores the use of synthetic endolysins designed for diverse in vivo applications, with potential implications for medical and veterinary practices in treating systemic and mucosal infections as well as nasal and skin infections.
This Research Topic covers the following focus areas:
1. Application of synthetic endolysins for preclinical and clinical evaluation to treat systemic infections.
2. Strategies to evade or dampen the adverse immune response induced by the generation of neutralizing antibodies, which may reduce in vivo endolysin activity.
3. Engineering endolysins to target specific organs and tissues after oral administration.
4. Engineering endolysins to improve half-life, bio-distribution, and pharmacokinetics.
We welcome the submission of Original Research Articles, Reviews, Mini Reviews, Methods, Perspective and Systematic Reviews.
Keywords:
Endolysin, Synthetic biology, Engineering, Bacterial pathogen, Infectious diseases, Systemic infection, Preclinical and clinical trials
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.
The overuse of antibiotics fuels the antimicrobial resistance (AMR) dilemma, which has complicated clinical treatment of bacterial illnesses and jeopardized worldwide public health. Action must be taken immediately to address the AMR issue.
As novel antimicrobial agents, bacteriophages (phages) and their lytic enzymes have been extensively explored. Phages are the most prevalent biological entities, which are found in every part of the biosphere, including soil, the atmosphere, marine ecosystems, and the human body.
The ability of phages to specifically infect and rapidly destroy their hosts during their lytic life cycles is a notable advantage over antibiotics. Endolysins are lytic enzymes produced by phages to degrade the bacterial cell wall, thereby releasing replicated progeny virions. For billions of years, phages have utilized endolysins for this specific function. This makes endolysins strong candidates for use as alternatives to antibiotics.
Synthetic biology has been employed to improve the specificity and catalytic activity of endolysins by fusing them with various antimicrobial peptides and by swapping or shuffling between different endolysins. Engineered endolysins have significant potential for in vitro applications. In vivo uses, however, demonstrate varying levels of therapeutic effectiveness.
While several endolysins have been successful in topical treatments, such as for skin bacterial infections, the systemic use of endolysins remains challenging. Endolysins are easily degraded by stomach acids and proteases when taken orally. Another issue with systemic and mucosal administration is the adverse immunological response triggered by the production of neutralizing antibodies, which could reduce endolysin activity in vivo.
Further exploration of endolysins is required to overcome these obstacles and to support their clinical applications in vivo. Endolysins encapsulated in liposomes or alginate hydrogels using nanoparticles may be a feasible solution to overcome the delivery challenges.
This research topic explores the use of synthetic endolysins designed for diverse in vivo applications, with potential implications for medical and veterinary practices in treating systemic and mucosal infections as well as nasal and skin infections.
This Research Topic covers the following focus areas:
1. Application of synthetic endolysins for preclinical and clinical evaluation to treat systemic infections.
2. Strategies to evade or dampen the adverse immune response induced by the generation of neutralizing antibodies, which may reduce in vivo endolysin activity.
3. Engineering endolysins to target specific organs and tissues after oral administration.
4. Engineering endolysins to improve half-life, bio-distribution, and pharmacokinetics.
We welcome the submission of Original Research Articles, Reviews, Mini Reviews, Methods, Perspective and Systematic Reviews.
Keywords:
Endolysin, Synthetic biology, Engineering, Bacterial pathogen, Infectious diseases, Systemic infection, Preclinical and clinical trials
Important Note:
All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.